• Asian Pacific Journal of Cancer Prevention
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• v.17 no.8
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• pp.3929-3937
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• 2016

Gastric cancer (GC) is a major health problem worldwide and is one of the ten most commonly diagnosed cancers in Jordan. GC is usually diagnosed at late aggressive stages in which treatment options are limited. Recently, heat shock proteins (HSPs) were found to be overexpressed in a wide range of malignancies have been considered as promising candidate biomarkers for GC. The aim of this study was to investigate pathogenic roles of a panel of cytosolic HSPs including HSP90, HSP70, HSP60 and HSP27 in GC. Immunohistochemistry was used to assess the level of expression of these proteins in archived tumor samples (N=87) representing various pathological characteristics of GC. HSP90, HSP60 and HSP27 were expressed abundantly in gastric tumors. On the other hand, HSP70 was reduced significantly and also found to be associated with Helicobacter pylori infection in tissues collected from GC patients. Furthermore, HSP27 was found to be associated with the level of differentiation. Our findings indicate a role of HSP70 as a potential prognostic biomarker, patients harboring positive HSP70 expression displaying worse disease free survival than those with negative HSP70 expression. Differential expression of HSPs may play crucial roles in the initiation and progression of GC, and could be exploited as future therapeutic targets.

• Asian-Australasian Journal of Animal Sciences
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• v.17 no.11
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• pp.1496-1500
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• 2004

In the mammalian ovary the follicular fluid contains proteins and peptides which play an important role in growth, development and maturation of oocytes. The gonadotropins and some other factors work synergistically and regulate ovarian functions. In the present study the effect of follicular fluid proteins (FFP) and gonadotropins on progesterone secretion by granulosa cells (GC) from buffalo ovary, was investigated during culture. The follicular fluid was collected from small (<5 mm), and medium (5-8 mm) follicles obtained from buffalo ovaries. The follicular fluid from medium follicles was fractionated with ammonium sulphate at 80% saturation. The precipitated protein fraction was further resolved in to minor (peaks I, III) and major (peak II) proteins using gel filtration (Sephadex G-200). The FFP from small follicles and major FFP (peak II) at a dose of 200 $\mu$g/well, significantly stimulated progesterone secretion by pooled GC (3${\times}10^{5}$ cells/2 ml medium/well). The minor FFP did not show any stimulatory effect. There was a significant increase in progesterone secretion by pooled GC in presence of FFP and LH (10 ng/well), however, FSH (20 ng/well) with FFP exhibited an inhibitory effect. The major FFP and gonadotropins were also studied for their effect on progesterone production by GC isolated from medium and large size follicles. The GC from medium follicles were more responsive to FSH and FFP whereas GC from large follicles exhibited enhanced progesterone secretion with LH and FFP. These results indicated that FFP have their own stimulatory effect and also act synergistically with gonadotropins. The significantly different response shown by GC, for steroid hormone secretion, is based on their stage of growth and differentiation. The purification and characterization of such steroidogenic proteins may help in elucidating their role in growth and differentiation of granulosa cells.

• Journal of Gastric Cancer
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• v.21 no.4
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• pp.439-456
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• 2021

Purpose: Gastric cancer (GC) has high morbidity and mortality and is a serious threat to public health. The flavonoid compound vitexin is known to exhibit anti-tumor activity. In this study, we explored the therapeutic potential of vitexin in GC and its underlying mechanism. Materials and Methods: The viability, migration, and invasion of GC cells were determined using MTT, scratch wound healing, and transwell assays, respectively. Target molecule expression was determined by western blotting. Tumor growth and liver metastasis were evaluated in vivo using nude mice. Protein expression in the tumor tissues was examined by immunohistochemistry. Results: Vitexin inhibited GC cell viability, migration, invasion, and epithelial-mesenchymal transition (EMT) in a dose-dependent manner. Vitexin treatment led to the inactivation of phosphatidylinositol-3-kinase (PI3K)/AKT/hypoxia-inducible factor-1α (HIF-1α) pathway by repressing HMGB1 expression. Vitexin-mediated inhibition in proliferation, migration, invasion and EMT of GC cells were counteracted by hyper-activation of PI3K/AKT/HIF-1α pathway or HMGB1 overexpression. Finally, vitexin inhibited the xenograft tumor growth and liver metastasis in vivo by suppressing HMGB1 expression. Conclusions: Vitexin inhibited the malignant progression of GC in vitro and in vivo by suppressing HMGB1-mediated activation of PI3K/Akt/HIF-1α signaling pathway. Thus, vitexin may serve as a promising therapeutic agent for the treatment of GC.

• Journal of Microbiology and Biotechnology
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• v.32 no.7
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• pp.938-948
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• 2022

Gastric cancers (GC) are generally malignant tumors, occurring with high incidence and threatening public health around the world. Circular RNAs (circRNAs) play crucial roles in modulating various cancers, including GC. However, the functions of circRNAs and their regulatory mechanism in colorectal cancer (CRC) remain largely unknown. This study focuses on both the role of circCOL1A2 in CRC progression as well as its downstream molecular mechanism. Quantitative polymerase chain reaction (qPCR) and western blot were adopted for gene expression analysis. Functional experiments were performed to study the biological functions. Fluorescence in situ hybridization (FISH) and subcellular fraction assays were employed to detect the subcellular distribution. Luciferase reporter, RNA-binding protein immunoprecipitation (RIP), co-immunoprecipitation (Co-IP), RNA pull-down, and immunofluorescence (IF) and immunoprecipitation (IP) assays were used to explore the underlying mechanisms. Our results found circCOL1A2 to be not only upregulated in GC cells, but that it also propels the migration and invasion of GC cells. CircCOL1A2 functions as a competing endogenous RNA (ceRNA) by sequestering microRNA-1286 (miR-1286) to modulate ubiquitin-specific peptidase 10 (USP10), which in turn spurs the migration and invasion of GC cells by regulating RFC2. In sum, CircCOL1A2 sponges miR-1286 to promote cell invasion and migration of GC by elevating the expression of USP10 to downregulate the level of RFC2 ubiquitination. Our study offers a potential novel target for the early diagnosis and treatment of GC.

• Journal of Animal Science and Technology
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• v.56 no.3
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• pp.9.1-9.8
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• 2014

This study was performed to investigate the effects of different forms of concentrate fed to Hanwoo steers on performance, carcass characteristics, and economic performance. Forty-two Hanwoo steers (average age of $5.1{\pm}0.8mo$. with body weight of $147.05{\pm}10.85kg$) were randomly allotted into FC (animals fed flakes for entire experimental period) and GC (animals fed grounded concentrate during growing and fattening phases followed by flaked concentrate during finishing phase) groups for 758 d after reaching an age of $30.0{\pm}0.82mo$. There was no difference in body weight (BW) or ADG between the treatments until fattening (15 ~ 22 mo.) phase. However, by finishing phase (23 ~ 30 mo.), the GC group (739.24 kg BW and 0.67 kg ADG) showed greater (P < 0.05) BW and ADG than the FC group (702.93 kg BW and 0.59 kg ADG). Steers in the GC group also showed greater (P < 0.05) BW and ADG than the FC group throughout the entire experimental period (5 ~ 30 mo.). There was no significant difference in carcass weight or backfat thickness between the treatments. M. Longissimus dorsi area of the GC group ($91.00cm^2$) was greater (P < 0.05) than that of the FC group ($83.59cm^2$). Marbling score and percentage of $1^{{+}{+}}$ meat quality grade were 14.0 and 48.0% higher in the GC group compared to the FC group. There was no significant difference in physicochemical characteristics, including moisture and crude protein levels, between the treatments. Gross income per head excluding operating expenses was 59.3% greater in the GC group (1,647,512 won) compared to the FC group (1,034,343 won).

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.20
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• pp.8923-8929
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• 2014

Background: Increasing evidence suggests that stromal monocarboxylate transporter 4 (MCT4) and carbonic anhydrase IX (CA IX) may play key roles in tumor development. However, their clinical value remains largely unexplored in gastric cancer (GC). The present study aimed to determine clinicopathological significance and prognostic values of stromal MCT4 and CA IX in GC. Materials and Methods: Specimens from 143 GC patients were immunohistochemically stained using polyclonal anti-MCT4 and anti-CA IX antibodies. Expression was correlated with patient clinicopathologic characteristics and survival data. Results: High stromal MCT4 expression was detected in 72 of 143 (50.3%) GCs and high CA IX in 74 (51.7%). Both high stromal MCT4 and CA IX were correlated with advanced TNM stage (p=0.000; p=0.000). High CA IX expression was positively related to depth of invasion (p=0.022) and positive lymph nodes (p=0.002) as well. Survival analysis indicated high expression of stromal MCT4 to be an independent factor in predicting poor overall survival (OS) (HR and 95%CI=1.962, 1.032-3.729, p=0.040) and disease free survival (DFS) (HR and 95%CI=2.081, 1.158-3.741, p=0.014) of GC patients. However, high CA IX expression exhibited no significant predictive value. Conclusions: These findings suggest that high expression of stromal MCT4 and CA IX proteins is significantly correlated with GC progression. High stromal MCT4 heralds worse outcome of GC patient, suggesting a novel candidate prognostic marker and therapeutic target.

• The Korean Journal of Physiology and Pharmacology
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• v.15 no.5
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• pp.273-277
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• 2011

Nitric oxide (NO) and atrial natriuretic peptide (ANP) may induce vascular relaxation by increasing the production of cyclic guanosine monophosphate (cGMP), an important mediator of vascular tone during sepsis. This study aimed to determine whether regulation of NO and the ANP system is altered in lipopolysaccharide (LPS)-induced kidney injury. LPS (10 $mg{\cdot}kg^{-1}$) was injected in the tail veins of male Sprague-Dawley rats; 12 hours later, the kidneys were removed. Protein expression of NO synthase (NOS) and neutral endopeptidase (NEP) was determined by semiquantitative immuno-blotting. As an index of synthesis of NO, its stable metabolites (nitrite/nitrate, NOx) were measured using colorimetric assays. mRNA expression of the ANP system was determined by real-time polymerase chain reaction. To determine the activity of guanylyl cyclase (GC), the amount of cGMP generated in response to sodium nitroprusside (SNP) and ANP was calculated. Creatinine clearance decreased and fractional excretion of sodium increased in LPS-treated rats compared with the controls. Inducible NOS protein expression increased in LPS-treated rats, while that of endothelial NOS, neuronal NOS, and NEP remained unchanged. Additionally, urinary and plasma NOx levels increased in LPS-treated rats. SNP-stimulated GC activity remained unchanged in the glomerulus and papilla in the LPS-treated rats. mRNA expression of natriuretic peptide receptor (NPR)-C decreased in LPS-treated rats, while that of ANP and NPR-A did not change. ANP-stimulated GC activity reduced in the glomerulus and papilla. In conclusion, enhancement of the NO/cGMP pathway and decrease in ANP clearance were found play a role in the pathogenesis of LPS-induced kidney injury.

• KSBB Journal
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• v.21 no.6 s.101
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• pp.410-413
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• 2006

The composition of two Bokbunja (Rubus coreanus Miquel) wines (one without mushroom extracts (wine A) and the other is with the extracts (wine B)) has been investigated to improve the quality of Bokbunja wine. The content of solid particle, acidity, crude ash, crude protein of the wine A were 10.5%, 1.36%, 0.45% and 0.05% and those of wine B were 7.4%, 0.54%, 0.31%, and 0.22%, respectively. Crude fat and crude fiber were not detected in both samples. To verify the flavor quality of Bokbunja wine, the volatile components from ethylether extracts of two wines were analyzed using GC/FID and GC/MS. A total number of 12 volatile flavor compounds (6 alcohols, 3 ketones, 1 acid, 1 ester and 1 anhydride) were identified in the two Rubus wines. The major volatile compounds of the wines were 2,3-butanediol, 2,5-furanedione, phenylethyl alcohol, and butanedioic acid and they might affect the major role in the unique flavor of Bokbunja wines.

• Parasites, Hosts and Diseases
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• v.53 no.6
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• pp.689-697
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• 2015

The tapeworm Taenia solium is an important human zoonotic parasite that causes great economic loss and also endangers public health. At present, an effective vaccine that will prevent infection and chemotherapy without any side effect remains to be developed. In this study, codon usage patterns in the T. solium genome were examined through 8,484 protein-coding genes. Neutrality analysis showed that T. solium had a narrow GC distribution, and a significant correlation was observed between GC12 and GC3. Examination of an NC (ENC vs GC3s)-plot showed a few genes on or close to the expected curve, but the majority of points with low-ENC (the effective number of codons) values were detected below the expected curve, suggesting that mutational bias plays a major role in shaping codon usage. The Parity Rule 2 plot (PR2) analysis showed that GC and AT were not used proportionally. We also identified 26 optimal codons in the T. solium genome, all of which ended with either a G or C residue. These optimal codons in the T. solium genome are likely consistent with tRNAs that are highly expressed in the cell, suggesting that mutational and translational selection forces are probably driving factors of codon usage bias in the T. solium genome.

• BMB Reports
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• v.51 no.5
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• pp.255-260
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• 2018

Wntless/GPR177 functions as WNT ligand carrier protein and activator of $WNT/{\beta}$-catenin signaling, however, its molecular role in gastric cancer (GC) has remained elusive. We investigated the role of GPR177 in gastric tumorigenesis and provided the therapeutic potential of a clinical development of anti-GPR177 monoclonal antibodies. GPR177 mRNA expression was assessed in GC transcriptome data sets (GSE15459, n = 184; GSE66229, n = 300); protein expression was assessed in independent patient tumor tissues (Yonsei TMA, n = 909). GPR177 expression were associated with unfavorable prognosis [log-rank test, GSE15459 (P = 0.00736), GSE66229 (P = 0.0142), and Yonsei TMA (P = 0.0334)] and identified as an independent risk predictor of clinical outcomes: GSE15459 [hazard ratio (HR) 1.731 (95% confidence interval; CI; 1.103-2.715), P = 0.017], GSE66229 [HR 1.54 (95% CI, 1.10-2.151), P = 0.011], and Yonsei TMA [HR 1.254 (95% CI, 1.049-1.500), P = 0.013]. Either antibody treatment or GPR177 knockdown suppressed proliferation of GC cells and sensitized cells to apoptosis. And also inhibition of GPR177 suppresses in vitro and in vivo tumorogenesis in GC cells and inhibits $WNT/{\beta}$-catenin signaling. Finally, targeting and inhibition of GPR177 with antibody suppressed tumorigenesis in PDX model. Together, these results suggest GPR177 as a novel candidate for prognostic marker as well as a promising target for treatment of GC patients.